Herpes simplex virus (HSV) is one of the most common viral infections in the world, affecting billions of people across the globe. While it can cause uncomfortable symptoms like painful blisters on the mouth or genitals, many people infected with this virus never develop any symptoms at all and may not even realize they carry it. Understanding this widespread infection can help remove the fear and stigma often attached to it, and knowing that effective treatments exist can make living with herpes a manageable part of life.

Epidemiology: A Global and Common Infection

Herpes simplex virus is remarkably widespread across the world. According to global health estimates, approximately 3.8 billion people under the age of 50, which represents about 64% of this age group globally, have herpes simplex virus type 1 (HSV-1) infection. This type is mainly responsible for what we commonly call oral herpes or cold sores around the mouth.^[2]

When it comes to genital herpes, the numbers are also significant. An estimated 520 million people aged 15 to 49 years worldwide, representing about 13% of this population, have herpes simplex virus type 2 (HSV-2) infection, which is the main cause of genital herpes.^[2] In the United States specifically, CDC estimates show that there were 572,000 new genital herpes infections in 2018 among people aged 14 to 49 years.^[3]

Looking at the American population more closely, research indicates that among Americans aged 14 to 49 years, approximately 53.9% are infected with HSV-1 and about 15.7% with HSV-2.^[16] Other sources suggest that about 12%, or roughly one in eight persons in this age group in the United States, has genital HSV-2 infection. However, as many as 90% of those infected are unaware that they have the virus.^[4]

More than 50% of the adult population in the United States has oral herpes, commonly called cold sores or fever blisters. Most people contract oral herpes during childhood by receiving a kiss from a friend or relative.^[4] This demonstrates how easily the virus spreads through everyday, non-sexual contact, particularly in the case of HSV-1.

An important finding from global research is that in 2020, an estimated 205 million people aged 15 to 49 experienced at least one symptomatic episode of genital herpes. This number highlights that while many carry the virus, only a fraction experience noticeable symptoms during any given year.^[2]

Causes: How Herpes Simplex Virus Enters and Stays in the Body

Herpes simplex virus infection is caused by two closely related but distinct types of viruses. Both HSV-1 and HSV-2 belong to the Alphaherpesviridae subfamily and share about 50% sequence similarity in their genetic makeup. The structure of these viruses consists of linear double-stranded DNA wrapped in an icosahedral capsid, which is a geometric protein shell approximately 100 to 110 nanometers in diameter, surrounded by a spiked outer layer called an envelope.^[5][6]

Traditionally, HSV-1 has been associated with infections of the mouth and face, while HSV-2 has been linked to genital infections. However, this distinction has become less clear over time. Recent research shows that either type can cause infection in either location. In fact, HSV-1 is now responsible for an increasing proportion of genital herpes cases, especially among young women and certain populations. Studies suggest that almost 80% of college students with genital herpes have HSV-1, probably due to high rates of oral sex in this group.^[6][16]

The virus enters the body through breaks in the skin or through mucous membranes, which are the moist tissues lining body openings such as the mouth, genitals, and eyes. Once inside, the virus attaches to cells using widespread receptors found on many cell types, including sensory neurons, which are nerve cells that transmit sensory information.^[1][6]

After entering the body, HSV begins making copies of itself using the host’s cells. This process is called viral replication. The immune system responds by mobilizing its defenses to limit the virus’s spread. However, what makes herpes simplex virus particularly challenging is its ability to establish latency, a state in which the virus remains dormant or sleeping in the body for life.^[1][4]

To avoid the immune system, HSV retreats along nerve pathways and hides in clusters of nerve cells called ganglia. In cases of genital herpes, the virus typically retreats to the sacral ganglion, located at the base of the spine near the tailbone. In oral or facial herpes, HSV finds its way to the trigeminal ganglion, located at the top of the spine. In these protected locations, the virus remains inactive for indefinite periods.^[4][6]

The latency phenomenon is similar to a sleep cycle. The virus returns to a safe haven and sleeps, sometimes for long periods. Unfortunately, while HSV is latent, various biological events can cause it to become active again. When reactivation occurs, the virus travels back along the nerve pathways to the skin, where it can cause symptoms again, though it doesn’t always produce noticeable signs.^[4]

Risk Factors: Who Is More Likely to Get Herpes

Risk factors for acquiring herpes simplex virus vary depending on the type of infection and the specific circumstances of exposure. Understanding these risk factors can help people take appropriate precautions.

For orolabial herpes, which affects the mouth area, risk factors include any activity that exposes a person to an infected individual’s saliva. This can happen through shared drinkware or cosmetics, or through mouth-to-mouth contact such as kissing. Since most people with oral herpes contract it during childhood or young adulthood from non-sexual contact, simply being kissed by a family member or friend who has the virus can lead to infection.^[3][5]

Anyone who is sexually active can get genital herpes. The major risk factors include having vaginal, anal, or oral sex with someone who has the infection. People who have multiple sexual partners or who start having sex at a young age face higher risk of exposure to HSV.^[3][4]

Participation in high-contact sports such as rugby, wrestling, mixed martial arts (MMA), and boxing increases the risk of a condition called herpes gladiatorum, which occurs when the virus is transmitted through skin-to-skin contact during these activities.^[5]

For herpetic whitlow, an infection of the fingers, risk factors in children include thumb sucking and nail biting when they have an active oral HSV-1 infection. In adults, particularly those in medical or dental professions, the risk comes from contact with infected saliva or lesions during patient care, though this has become less common with the use of gloves.^[5]

People with weakened immune systems, such as those with HIV or those taking immunosuppressive medications, face higher risks of severe HSV infections. This includes infections that can affect internal organs like the esophagus, lungs, and liver. These types of infections are more likely to affect people who are immunocompromised, meaning their immune systems don’t function at full strength.^[1]

For herpes encephalitis, a serious brain infection, certain genetic factors play a role. Mutations in genes involved in immune function, such as the toll-like receptor 3 (TLR-3) or UNC-93B genes, have been identified as major risk factors. These mutations inhibit normal immune responses that would typically help fight the virus.^[5]

The major risk factor for eczema herpeticum, a widespread and potentially serious skin infection, is having a condition that causes skin barrier dysfunction. This is commonly seen in people with atopic dermatitis (eczema), but also occurs with other skin conditions like Darier disease, Hailey-Hailey disease, mycosis fungoides, and various types of ichthyosis.^[5]

Symptoms: What Herpes Looks and Feels Like

Most people with herpes simplex virus have no symptoms or only very mild symptoms. Many aren’t aware they have the infection and can pass the virus to others without knowing. Up to 80% of herpes simplex infections are asymptomatic, meaning they produce no noticeable signs.^[2][6]

When symptoms do occur, they can include painful, recurring blisters or ulcers. The appearance and severity of symptoms often differ between the first episode of infection and later recurrent episodes. Symptoms may be different and often more severe during the first outbreak compared to subsequent ones.^[2]

For oral herpes, the most common symptoms are blisters, often called cold sores, on the lips or around the mouth. The skin may tingle, itch, or burn for up to 48 hours before the blisters actually appear. Some people develop a condition called herpetic gingivostomatitis when they first get infected, which causes sores inside the mouth along with other symptoms like fever and swollen lymph nodes. Rarely, sores can develop on or inside the nose, a condition known as nasal herpes.^[1][2]

For genital herpes, symptoms include blisters on and around the genitals, which may also appear on the buttocks or inner thighs. In the 48 hours before blisters appear, people may experience fever, headache, swollen lymph nodes, and itching or tingling in the affected area. The blisters typically appear as small bumps that develop into fluid-filled sores. When these sores are near the urethra, the opening through which urine exits the body, urination may cause a burning sensation.^[1][2][16]

Herpes sores usually appear as one or more blisters on or around the genitals, rectum, or mouth. This is known as having an outbreak. The blisters break open and leave painful sores that may take a week or more to heal. These sores and blisters are typically painful and may break open, ooze fluid, and then crust over before healing completely.^[2][3]

During the first infection, people may experience additional symptoms beyond just the blisters. These can include fever, body aches, sore throat in cases of oral herpes, headaches, and swollen lymph nodes near the infection site. People who experience an initial outbreak can have repeated outbreaks over time, though these recurrences are usually shorter and less severe than the first outbreak.^[2][3]

Mild symptoms may go unnoticed or be mistaken for other skin conditions like a pimple or ingrown hair. This is why most people don’t realize they have a herpes infection. Before symptoms appear, the skin may tingle, itch, or burn. This early warning sign is called prodrome.^[3][12]

Although genital herpes is a lifelong infection, the number of outbreaks typically decreases over time for most people. Some people may eventually stop having outbreaks altogether, though the virus remains in the body.^[3]

Prevention: How to Protect Yourself and Others

Preventing herpes simplex virus transmission requires awareness, precaution, and in some cases, medication. While there is no vaccine currently available for herpes, several strategies can significantly reduce the risk of getting or spreading the infection.

The only way to completely avoid sexually transmitted infections, including genital herpes, is to not have vaginal, anal, or oral sex. For people who are sexually active, being in a long-term mutually monogamous relationship with a partner who has been tested and does not have herpes can lower the risk of infection.^[3]

Using condoms correctly every time during sexual activity can reduce the risk of getting or spreading genital herpes. However, it’s important to understand that condoms don’t provide complete protection because herpes can be spread through contact with skin areas not covered by a condom. The virus can be present on areas of the genitals, buttocks, or thighs that a condom doesn’t cover.^[3]

People with herpes can take steps to prevent transmission to their partners. If someone knows they have herpes, they should always tell their sexual partners. This honest communication allows both partners to make informed decisions about their sexual health. Taking antiviral medication daily, known as suppressive therapy, can significantly reduce the likelihood of spreading the virus to partners.^[3][12]

It’s also crucial to avoid sexual contact during outbreaks when symptoms are present, as the risk of transmission is highest during these times. However, people should be aware that herpes can also spread during periods when no symptoms are visible. There are several days throughout the year when the virus may be on the surface of the skin without causing any noticeable symptoms, a phenomenon called asymptomatic shedding or subclinical shedding. Herpes can be passed through sexual contact during these times.^[4][7]

For oral herpes prevention, people should avoid kissing and sharing drinks, utensils, or personal items like lip balm with others when they have an active cold sore. Parents and caregivers with oral herpes should be especially careful not to kiss young children on the mouth when they have symptoms.^[3]

People should also be aware that oral herpes can be transmitted to the genitals through oral sex. If someone has oral herpes, they can pass the infection to a partner’s genitals during oral sex, even if they don’t have visible sores at the time. Using barriers like dental dams or condoms during oral sex can reduce this risk.^[3]

For healthcare workers, particularly those in medical and dental fields, using gloves and following proper infection control procedures can prevent herpetic whitlow, an infection of the fingers that can occur from contact with infected saliva or lesions.^[5]

Athletes in high-contact sports should avoid participating when they have active lesions and should practice good hygiene, including showering immediately after practice or competition and not sharing towels or equipment.^[5]

Pathophysiology: How Herpes Affects the Body

Understanding how herpes simplex virus operates within the body helps explain why the infection behaves the way it does and why it cannot currently be cured. The virus has evolved sophisticated mechanisms to survive in the human body for a lifetime.

HSV-1 and HSV-2 are characterized by unique biological properties that set them apart from many other viruses. The first is neurovirulence, which is the capacity to invade and replicate in the nervous system. This ability to infect nerve cells is central to how the virus establishes persistent infection.^[6]

The second key property is latency. After the initial infection of skin or mucous membrane cells, the virus establishes and maintains latent infection in nerve cell ganglia near the site of infection. In orofacial HSV infections, the trigeminal ganglia are most commonly involved. In genital HSV infection, the sacral nerve root ganglia, specifically those labeled S2 through S5, are the typical hiding places.^[6]

During latency, the virus remains in the ganglion in an inactive state for an indefinite period. The DNA of the virus is present in the nerve cells, but the virus is not actively reproducing. The immune system cannot detect or eliminate the virus during this dormant phase because the virus has essentially gone into hiding.^[4]

The third property is reactivation. Various stimuli can trigger the reactivation and replication of latent HSV. These triggers may include fever, physical or emotional stress, sunlight exposure, menstruation, trauma to the skin, and other factors. When reactivation occurs, the virus travels along the nerve pathways back to the skin or mucous membranes, always in the area supplied by the ganglia where latency was established. This can result in either noticeable recurrent infection with symptoms or covert shedding of the virus without visible signs.^[6]

In immunocompetent people who have equal risk of acquiring both types of virus, HSV-1 reactivates more frequently in the oral region rather than the genital area. On the other hand, HSV-2 reactivates eight to ten times more commonly in the genital region than in the orolabial region. This preference explains why certain types of herpes tend to recur in specific body locations.^[6]

When the virus reactivates and reaches the skin, it infects epithelial cells, which are the cells that form the outer layer of skin. The virus enters these cells and uses their machinery to replicate. This replication process damages and eventually kills the infected cells, leading to the formation of the characteristic blisters and sores associated with herpes outbreaks.^[1]

The body’s immune response to the infection also contributes to symptoms. When the immune system detects viral activity, it sends immune cells to the affected area. This response causes inflammation, which contributes to the redness, swelling, and pain associated with herpes lesions. The immune response eventually brings the outbreak under control, and the skin heals. However, the virus retreats back to the nerve ganglia, where it remains dormant until the next reactivation.^[4]

The frequency of viral reactivation varies greatly among individuals. Some people experience frequent outbreaks, while others may go years without symptoms. Research has shown that many reactivation events occur without producing visible lesions. During these periods of asymptomatic shedding, the virus is present on the skin surface and can be transmitted to others, but the person carrying the virus has no signs or symptoms to alert them to the viral activity.^[4][7]

Studies using daily genital swab samples have detected HSV-2 on a median of 12 to 28% of days among those who had previous outbreaks, and on about 10% of days among those with asymptomatic infection who had never experienced noticeable outbreaks. Many of these episodes occur without any symptoms.^[7]